ClinVar

Description

Variant summary: CFTR c.4307_4320del14 (p.Leu1436HisfsX21) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., p.Ser1455X and p.Gln1476X). This variant is likely to disrupt the ABC transporter-like domain at the C-terminal of the encoded protein. The variant was absent in 245714 control chromosomes (gnomAD). To our knowledge, no occurrence of c.4307_4320del14 in individuals affected with Cystic Fibrosis and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.